tbuckley/cabot-search huggingface dataset:
386 Complete/near-complete itch response observed in adult and adolescent patients with moderate-to-severe atopic dermatitis initiating dupilumab treatment in real-world practice
Authors: Neal Bhatia, Charles W Lynde, Luz Fonacier, Tingting Tian, Kwinten Bosman, Andrew  Korotzer
Journal: British Journal of Dermatology (2023)

Abstract Chronic itch (pruritus) is a defining characteristic of atopic dermatitis (AD) and is a significant contributor to poor quality of life in patients. A Pruritus/Peak Pruritus Numerical Rating Scale (NRS) score of 0/1 could be considered a complete or near-complete itch response. This study aims to report Pruritus NRS and Overall Disease Severity (ODS) score of 0/1 over time in patients older than 12 years with moderate-to-severe AD initiating dupilumab treatment in real-world practice. Patients aged ≥12 years with moderate-to-severe AD, initiating real-world dupilumab treatment for AD per approved prescribing information in the USA and Canada, were eligible for entry into PROSE (NCT03428646). Enrolled patients received their first dose of dupilumab at the baseline visit; there were no restrictions on post-baseline dupilumab dosing changes, or concomitant medication use; patients were encouraged to stay in the study if they discontinued dupilumab. Data presented are from an interim analysis (data cut taken as of November 2022); only ≥36 months of patient experience in PROSE at the time of interim analysis is reported. No formal hypothesis testing was performed; descriptive statistics are presented. Among 857 patients [mean (SD) age 40.1 (17.9) years and 42% male], mean (SD) duration of dupilumab treatment was 23.1 (13.7) months. At Month 36, 185 patients (21.6%) had discontinued from the study; the main reason was withdrawal of consent by the patient (76 patients, 8.9%). The proportion of patients with available observations reporting a Pruritus NRS score of 0/1 increased from baseline (2.7%) to Month 3 (28.1%) and continued to increase up to Month 36 (56.3%). Similarly, the proportion of patients with a clinician-reported ODS score of 0/1 also increased from baseline (2.2%) to Month 3 (39.8%) and up to Month 36 (65.1%). Safety was consistent with the known dupilumab safety profile. In this interim analysis of PROSE, a majority of patients reported a complete/near-complete pruritus response and overall disease severity response over a 36-month period.
432 Comparative treatment persistence of different advanced-therapies in patients with atopic dermatitis
Authors: Eric Sanfilippo, Sneha Iyer, Jonathan I Silverberg
Journal: British Journal of Dermatology (2023)

Abstract Multiple advanced therapies are used to treat atopic dermatitis (AD), each with different efficacy, safety, tolerability, accessibility and treatment success that can affect treatment persistence. Little is known about how treatment persistence rates compare between different therapies. We compared treatment persistence for subcutaneous dupilumab, oral cyclosporine, mycophenolate, and upadacitinib, and narrowband ultraviolet B (NB-UVB) treatment of AD. A retrospective observational study was performed of patients with physician-diagnosed atopic AD from a large metropolitan tertiary care medical center. Medical records were reviewed for race, ethnicity, disease severity and use of therapies from 10/01/2015 to 10/1/2021. The AD cases were identified using Hanifin–Rajka criteria. Drug persistence was assessed using proportion of patients who discontinued therapy and median time to discontinuation. Chi-square tests were used to assess if there were differences in drug discontinuation rates by advanced therapy. Overall, 766 patients with AD were identified, including 139 (18.1%) prescribed dupilumab, 10 (1.3%) cyclosporine, 21 (2.7%) mycophenolate, 5 (0.7%) upadacitinib and 64 (8.4%) NB-UVB; no patients were treated with methotrexate. Drug persistence was highest for upadacitinib (100%), followed by dupilumab (86.3%), mycophenolate (38.1%), cyclosporine (30.0%) and NB-UVB (12.5%) (Chi-square, P &amp;lt; 0.0001). Highest median (days) time to discontinuation was observed with dupilumab (638), followed by cyclosporine (539), mycophenolate (274) and NB-UVB (167). Lack of efficacy was the most common reason for discontinuation of dupilumab, cyclosporine, mycophenolate and NB-UVB alike. Discontinuation due to adverse-events was highest for cyclosporine (42.9%), followed by dupilumab (31.6%), mycophenolate (30.8%) and NB-UVB (16.1%). Dupilumab had the most patients who discontinued due to disease improvement and no longer requiring advanced-therapy (21.1%). Our data suggest that drug persistence varies substantially across different advanced therapies for AD. Recently approved advanced therapies, including dupilumab and upadacitinib, showed the highest proportion of drug persistence.
430 Comparison of effectiveness of topical treatments for atopic dermatitis
Authors: Sabiha Uddin, Britton Upchurch, Rithi J Chandy, Steven R Feldman
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) is a chronic inflammatory condition that affects 15% of children and 7.3% of adults in the USA. While topical corticosteroids (TCs) and topical calcineurin inhibitors (TCIs) are considered the mainstay of topical treatments for AD management, long-term use is cautioned due to possible adverse effects (AEs). We present and review the efficacy and safety of new FDA-approved topical agents, topical agents currently in clinical trials, and TCs and TCIs that are currently available for AD management. We also present and compare the safety and efficacy of new and old FDA-approved topical agents, along with other topical treatments that are currently in clinical trials for AD management. An extensive review of the literature was performed using the PubMed, Cochrane, Scopus and ClinicalKey databases with year parameters set between 2014 and 2022. Search keywords included ‘atopic dermatitis’, ‘topical treatments’, ‘comparison’, ‘effectiveness’, ‘new topical treatments for AD’, ‘JAK inhibitors’, ‘PDE-4 inhibitors’, ‘delgocitinib’, ‘crisaborole’ and ‘tapinarof’. We identified four topical drug classes that are efficacious in treating AD: corticosteroids, calcineurin inhibitors, phosphodiesterase-4 (PDE-4) inhibitors and aryl hydrocarbon receptor agonists. Criteria for treatment success were an IGA score of 0 or 1 and improvement ≥2 grades from baseline. Treatment varied among studies from 2 to 24 weeks. Topical corticosteroids were the most effective after adjusting for vehicle (0.05% clobetasol propionate emulsion foam, 38%; 0.1% clocortolone pivalate, 31.6% IGA reduction), followed by tapinarof 1% cream with 29% of patients achieving treatment success, TCIs (0.03% tacrolimus ointment, 24.8%; 1% pimecrolimus cream, 32.1% vehicle-adjusted achieving IGA of ≤2) and PDE-4 inhibitors (2% crisaborole ointment, 10.4%). Tapinarof was the most efficacious in treating AD. There is a lack of head-to-head trials for topical treatments for AD. Due to the tremendous burden of AD on patients’ physical and mental health, there is a need for additional therapies.
399 Pooled safety analysis of lebrikizumab in patients with uncontrolled asthma from three randomized clinical trials
Authors: Jonathan Corren, Stanley J Szefler, April W   Armstrong, Chitra R Natalie, Ralph  Zitnik, Fangyi Zhao, Kimberly Siu, Peter A   Lio, Robert J Mourey
Journal: British Journal of Dermatology (2023)

Abstract LAVOLTA (L)I, LII and ACOUSTICS were randomized, placebo-controlled, double-blinded, Phase 3 trials of lebrikizumab, a monoclonal antibody targeting interleukin-13, in patients with uncontrolled asthma (LI, NCT01867125; LII, NCT01868061; ACOUSTICS, NCT01875003). These studies failed to provide consistently significant efficacy results in uncontrolled asthma. This study aims to report pooled safety analysis of lebrikizumab in patients during the 52-week placebo-controlled period from the three clinical trials. Adults in LI and LII, adolescents (12–17 years) in ACOUSTICS, with uncontrolled asthma, prebronchodilator forced expiratory volume in 1 s 40–90% predicted and stable background therapy were randomized 1 : 1 : 1 to lebrikizumab 125 or 37·5 mg or placebo (PBO) subcutaneously once every 4 weeks. Safety analyses were based on all patients who received at least one dose of study drug, with patients grouped by assigned treatment. Safety was assessed using summary of adverse events (AEs). The proportions of patients who experienced treatment-emergent AEs [combined lebrikizumab doses (LEB), 1281 (77%) of 1661 patients vs. PBO, 650 (78%) of 883 patients], serious AEs (7.6% vs. 8.5%) and AEs leading to study drug discontinuation (3.4% vs. 3.6%) were similar between LEB and PBO. One death occurred in the PBO group. Similar frequencies of key safety events, including conjunctivitis (LEB, 1.6%; PBO, 1.7%), infections and infestations (LEB, 51.6%; PBO, 50.7%), and eosinophil-related disorders (LEB, 0.2%; PBO, 0.2%) were noted; higher frequency of eosinophilia (&amp;gt;500 eosinophils/mm3) was reported (LEB, 1.1%; PBO, 0%). The safety profile was similar between lebrikizumab and placebo in adults and adolescents with uncontrolled asthma.
390 Efficacy and safety of roflumilast cream 0.15% in adults and children aged ≥6 years with mild to moderate atopic dermatitis in two phase 3 trials (INTEGUMENT-1 and INTEGUMENT-2)
Authors: Eric Simpson, Lawrence Eichenfield, Melinda  Gooderham, Mercedes E Gonzalez, Adelaide Hebert, Kim Papp, Vimal Prajapati, David Krupa, Patrick Burnett, David Berk, Robert Higham
Journal: British Journal of Dermatology (2023)

Abstract Roflumilast is a selective, highly potent phosphodie­sterase 4 inhibitor under investigation as a nonsteroidal, once-daily cream for treatment of atopic dermatitis (AD). INTEGUMENT-1 (n = 654; NCT04773587) and INTEGUMENT-2 (n = 683; NCT04773600) were identical phase 3 randomized controlled trials conducted in patients with AD aged ≥6 years with baseline Eczema Area and Severity Index (EASI) score ≥5 and Validated Investigator Global Assessment-AD (vIGA-AD) score of mild or moderate. Patients were randomized 2 : 1 to apply once-daily roflumilast cream 0.15% or vehicle for 4 weeks. The primary efficacy endpoint was vIGA-AD Success [defined as score of 0 (clear) or 1 (almost clear) with 2-grade improvement from baseline] at Week 4. Secondary endpoints included 75% improvement in EASI (EASI-75). At Week 4, significantly more roflumilast-treated than vehicle-treated patients achieved vIGA-AD Success (INTEGUMENT-1: 32.2% vs. 15.2%; P &amp;lt; 0.0001; INTEGUMENT-2: 28.9% vs. 12.0%; P &amp;lt; 0.0001) and EASI-75 (INTEGUMENT-1: 43.2% vs. 22.0%; P &amp;lt; 0.0001; INTEGUMENT-2: 42.0% vs. 19.7%; P &amp;lt; 0.0001). Incidence of treatment-emergent adverse events (AEs) was low in both arms, with most assessed as mild to moderate in severity. No AE occurred in more than 3.5% of patients in either arm with low rates of application site pain in both the roflumilast- and vehicle-treated patients (INTEGUMENT-1: 2.1% vs. 0.5%; INTEGUMENT-2: 0.9% vs. 0.9%). Local tolerability was favorable with &amp;gt;90% of roflumilast-treated patients reporting no or mild sensation across arms in both trials at any timepoint. Once-daily roflumilast cream 0.15% improved AD across multiple efficacy endpoints while demonstrating favorable safety and tolerability in two phase 3 trials.
400 Efficacy of lebrikizumab in patients who did not achieve protocol-defined criteria for response after initial 16 weeks of therapy
Authors: Emma Guttman-Yassky, David Rosmarin, Jacob P Thyssen, Stephan Weidinger, Thomas  Bieber, Hany Elmaraghy, Amber Reck  Atwater, Evangeline Pierce, Chenjia  Xu, Helena Agell Gimeno, Eric Simpson, Robert J Mourey
Journal: British Journal of Dermatology (2023)

Abstract Lebrikizumab demonstrated robust efficacy during the first 16 weeks of treatment in ADvocate1 and ADvocate2. This study aims to describe the 52-week results of lebrikizumab-treated patients who did not meet the protocol-defined criteria for response at 16 weeks of treatment. During the induction period, patients were randomized 2 : 1 to lebrikizumab 250 mg or placebo every 2 weeks (Q2W) for 16 weeks. Protocol-defined criteria for response were characterized as achieving a 75% Eczema Area and Severity Index (EASI75) or an Investigator’s Global Assessment of 0 or 1 (IGA 0,1) with a ≥2-point improvement and without rescue medication use. At Week 16, patients from the lebrikizumab treatment arm, who did not reach the criteria for response, were assigned to the Escape arm (n = 215). These patients continued to receive lebrikizumab 250 mg Q2W for an additional 36 weeks. Endpoints and measurements included at week 52 were EASI75, EASI90, IGA (0,1) and pruritus. Pruritus was assessed using an 11-point Pruritus Numeric Rating Scale (NRS). Data are presented as observed results with no imputation for missing data. Pooled results for patients who did not respond to lebrikizumab and entered the escape arm show 36.1% achieved IGA (0,1) with 2-point improvement at Week 52. In the same population, 75.5% achieved EASI75, 44.2% achieved EASI90 and 66.4% reported 4-point improvement in Pruritus NRS. These results suggest that patients, who do not achieve protocol-defined response at 16 weeks of treatment, can be slow responders and derive benefit from continuing long-term therapy with lebrikizumab.
405 Understanding patient experience and factors influencing patient preference in the treatment of moderate-to-severe atopic dermatitis through in-depth qualitative patient interviews
Authors: Steven R Feldman, Annie Guerin, Marjolaine  Gauthier-Loiselle, Ami J Claxton, Yan  Meng, Nisha C Hazra, Sanjeev Balu
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) can enormously affect the lives of patients and their caregivers. Treatments for moderate-to-severe AD include phototherapy, topical and systemic corticosteroids, other immunosuppressive agents and biologic therapies. These treatments offer varied levels of efficacy, safety, response times and modes of administration. Patient preferences for these treatment options and attributes influencing their treatment choice are not well characterized. This qualitative interview-based study evaluated treatment attributes important to adult patients with moderate-to-severe AD providing a basis for a future quantitative discrete choice experiment (DCE). Semi-structured interviews were conducted in adults (≥18 years) recruited via a panel of geographically and demographically diverse patients with AD in the USA. Inclusion required (i) diagnosis of AD for at least one year, (ii) inadequate response to prior topical therapy and (iii) self-reported moderate-to-severe AD or experience with systemic therapy. One-on-one, in-depth 60-min phone interviews were conducted by a trained interviewer in AD real-word evidence studies. Subjects with experience with systemic therapy for AD were queried concerning their involvement in initiating, logistics of and general experience with their most recent systemic treatment. Finally, participants were asked to rate the importance (on a 1–5 scale with 5 being the most important) of 17 attributes that could play a role in their treatment decision-making; these attributes were identified from a targeted literature review and expert dermatologist clinical input. Attributes included treatment efficacy, adverse events and treatment logistics. Interviews are ongoing, and results will be ready and presented in the poster upon acceptance. Findings from the interviews will shed light on recent patient experience with treatments for moderate-to-severe AD and elucidate the treatment attributes that most impact patient treatment preferences. These results will guide the design of a subsequent DCE survey, which will help quantify the relative importance of the treatment attributes identified herein.
401 Safety and efficacy of lebrikizumab in adolescent patients with moderate-to-severe atopic dermatitis: an open-label study
Authors: Amy Paller, Carsten Flohr, Lawrence F Eichenfield, Alan Irvine, Ana  Pinto-Correia, Chitra R Natalie, Evangeline  Pierce, Sarah Reifeis, Renata Gontijo Lima, Vivian Laquer, Stephan  Weidinger, Nadine Isho
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) can greatly impact quality of life in adolescents, and improved management is needed. Lebrikizumab, a high-affinity monoclonal antibody targeting interleukin (IL)-13, demonstrated clinical benefit in Phase 3 trials: ADvocate1, ADvocate2 and ADhere. This study aims to report 52-week safety and efficacy outcomes from ADore (NCT04250350), a Phase 3, open label study of lebrikizumab in adolescent patients with moderate-to-severe AD. Eligible adolescents (n = 206) (≥12 to &amp;lt;18 years; weighing ≥40 kg) received 500-mg loading doses at baseline and Week 2, and 250-mg lebrikizumab subcutaneous injections every 2-weeks (Q2W) for 52-weeks. Safety was monitored using adverse events (AEs), AEs leading to treatment discontinuation, vital signs and laboratory testing. Efficacy analyses included Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI). A total of 172 patients completed the treatment period. Low frequencies of AEs leading to treatment discontinuation (2.4%) and SAEs (2.4%) were reported. Overall, 134 (65.0%) patients reported at least one treatment-emergent adverse event, most being mild or moderate in severity, including 14 (6.8%) conjunctivitis events. Efficacy was rapid, with 14.4% achieving IGA (0,1) at Week 4, increasing to 46.3% at Week 16 and 62.6% at Week 52. The EASI-75 was 28.6% at Week 4, 73.2% at Week 16, and 81.9% at Week 52. The mean percent improvement from baseline to Week 52 in EASI was 86.0%. Lebrikizumab open-label 250-mg Q2W had a safety profile in adolescents with moderate-to-severe AD, which was consistent with previous trials, with 2.4% treatment discontinuation due to AEs. Lebrikizumab demonstrated efficacy, with 81.9% of patients achieving EASI-75 and 62.6% achieving IGA (0,1) at Week 52.
409 Efficacy and safety of upadacitinib in adults and adolescents with moderate-to-severe atopic dermatitis: subgroup analysis of the Measure Up 1, Measure Up 2 and AD Up phase 3 clinical trials at 52 weeks
Authors: Amy S Paller, Pedro Mendes-Bastos, Lawrence F   Eichenfield, Weily Soong, Peter  Lio, Vimal H Prajapati, Andrew M Platt, Eliza  Raymundo, John Liu, Barry Ladizinski, Jacob P Thyssen
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous morphology and intense pruritus. Previous clinical trials have demonstrated that upadacitinib (UPA) was superior to placebo (PBO) in the treatment of moderate-to-severe AD. Here, we analyse the efficacy and safety of UPA across 52 weeks in adolescent and adult subgroups from three phase 3 studies. Patients were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30) or PBO orally once daily, either alone or with concomitant topical corticosteroids. After 16 weeks, patients in the PBO group were randomized to the UPA15 or UPA30 groups. For both adolescent and adult subgroups at 52 weeks, the proportion of responders in the UPA15 and UPA30 groups was: ≥70% and 83% for EASI75, ≥31% and 47% for vIGA-AD 0/1 and ≥37% and 61% for Worst Pruritus Numeric Rating Scale improvement ≥4. Children’s Dermatology Life Quality Index (CDLQI) 0/1 was achieved by ≥15% (UPA15) and ≥28% (UPA30) of adolescents aged 12 to &amp;lt;16 years; DLQI 0/1 was achieved by ≥18% (UPA15) and ≥38% (UPA30) of adolescents aged 16 to &amp;lt;18 years and ≥30% (UPA15) and ≥45% (UPA30) of adults. Hospital Anxiety and Depression Scale (HADS-A and HADS-D) &amp;lt;8 was achieved in ≥28% of adolescents and ≥45% of adults for both treatment groups. Rates of serious adverse events (AEs) and serious AEs leading to discontinuation at week 52 were similar for both adolescents and adults. UPA15 and UPA30 responses in moderate-to-severe AD across 52 weeks were similar between adolescents and adults, with acceptable safety outcomes in both populations.
388 Efficacy and safety of roflumilast foam 0.3% in patients with seborrheic dermatitis in a phase 3 trial: assessment of pruritus
Authors: Andrew Blauvelt, Zoe D Draelos, Melinda  Gooderham, Edward Lain, Angela Y Moore, Kim A Papp, Matthew Zirwas, David Krupa, Patrick Burnett, David R Berk, David H Chu
Journal: British Journal of Dermatology (2023)

Abstract Itch is a major complaint among patients with seborrheic dermatitis (SD). Roflumilast is a selective, nonsteroidal, highly potent phosphodiesterase-4 inhibitor under investigation as a once-daily foam for treatment of SD. This phase 3 randomized, parallel-group, double-blind, vehicle-controlled trial (NCT04973228) was conducted in patients ≥9 years old with at least moderate SD affecting scalp and/or nonscalp areas. Patients were randomized 2 : 1 to apply once-daily roflumilast foam 0.3% (n = 304) or vehicle (n = 153) for 8 weeks. The primary efficacy endpoint was Investigator Global Assessment (IGA) success (IGA of Clear or Almost Clear plus ≥2-grade improvement from baseline) at Week 8. Secondary efficacy endpoints included Worst Itch Numeric Rating Scale (WI-NRS), which was completed daily by patients. Safety and local tolerability were also evaluated. Overall, significantly more roflumilast-treated patients than vehicle-treated patients achieved IGA success (79.5% vs. 58.0%; P &amp;lt; 0.0001) and IGA status of Clear (50.6% vs. 27.7%; P &amp;lt; 0.0001) at Week 8. Significantly greater percentages of roflumilast- than vehicle-treated patients had ≥4-point improvement on WI-NRS at Weeks 2 (32.7% vs. 15.5%; P = 0.0016), 4 (47.6% vs. 29.1%; P = 0.0007) and 8 (62.8% vs. 40.6%; P = 0.0001). Greater improvement in itch was observed among roflumilast-treated patients as early as 48 h after the first application (mean percent change from baseline: −27.87% vs. −13.11%; nominal P = 0.0024). Local tolerability and safety were favorable. Once-daily roflumilast foam provided improvement across multiple efficacy endpoints including rapid itch improvement, while demonstrating favorable safety and tolerability.
368 Impact of a digital atopic dermatitis educational intervention on Hispanic patients and family members
Authors: Luis F Andrade, MaryJo Bekhash, Siri  Choragudi, Juan M Gonzalez, Rodrigo  Valdes, Gil Yosipovitch
Journal: British Journal of Dermatology (2023)

Abstract With the increasing incidence of atopic dermatitis (AD) in the USA, the highest prevalence of AD being found in Hispanic countries, and the rising Hispanic-American population, educational resources on eczema focused on Spanish-speaking populations are needed more than ever. As such, the primary goal of this project was to assess the beneficial impact of an educational intervention conducted through a virtual platform for Hispanic individuals living with AD. Utilizing WhatsApp, the study enrolled 55 participants diagnosed with AD and/or parents of children diagnosed with AD. Participants were enrolled in a 7-day educational module with daily topics on AD health knowledge. A health knowledge survey was administered prior to the educational program, upon completion of the program and 1 month after completion. The program found a 14% increase in AD health knowledge upon completion of the program (P &amp;lt; 0.001). Most importantly, there was no significant difference found between the health knowledge survey submitted at program completion and 1 month after completion, signaling that health knowledge taught through the course was successfully retained by participants (P = 0.29). Qualitative themes involving atopic disease were additionally explored through group discussions, including mental health and peer stigma. This study is the first of its kind in dermatology utilizing the WhatsApp format. The success of retained health knowledge regarding AD demonstrates that future virtual endeavors can be effective methods of patient education overall, and be accessible interventions for populations that might not have ease of access to major medical centers, are in rural areas and/or in the international setting.